Humoral immune responses in Cr2-/- mice:: Enhanced affinity maturation but impaired antibody persistence
Humoral immune responses in Cr2-/- mice:: Enhanced affinity maturation but impaired antibody persistence
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DOI：
10.4049/jimmunol.164.9.4522
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发表时间：
2000-05-01
影响因子：
4.4
通讯作者：
Kelsoe, G
中科院分区：
文献类型：
--
作者：
Chen, ZB;Koralov, SB;Kelsoe, G
Cr2基因座的破坏导致CD21/CD35缺乏，进而引起体液免疫应答受损。在本研究中，我们详细阐述了CD21/CD35在针对与鸡γ -球蛋白偶联的半抗原（4 - 羟基 - 3 - 硝基苯）乙酰基的抗体应答中的作用。令人惊讶的是，Cr2（-/-）小鼠对明矾中低剂量的这种抗原产生了显著的抗体应答和生发中心（GC）反应，尽管与Cr2（+/-）和C57BL/6对照相比，其应答程度大幅降低。增加抗原剂量可部分纠正这种缺陷。对生发中心B细胞体细胞遗传学的原位研究表明，VDJ超突变不需要CD21/CD35，并且Cr2（-/-）小鼠在初次应答的生发中心后阶段表现出血清抗体亲和力成熟增强。另一方面，Cr2（-/-）小鼠显示出血清抗体和长寿抗体形成细胞加速丢失。这些观察结果表明，由CD21介导的B细胞活化/存活信号和/或CD21/CD35对抗原的保留在血清抗体的产生、质量和维持中起重要作用。《免疫学杂志》，2000年，164卷：4522 - 4532页。
Deficiency in CD21/CD35 by disruption of the Cr2 loci leads to impaired humoral immune responses. In this study, we detail the role of CD21/CD35 on Ab responses to the hapten (4-hydroxy-3-nitrophenyl)acetyl conjugated to chicken gamma-globulin. Surprisingly, Cr2(-/-) mice generate significant Ab responses and germinal center (GC) reactions to low doses of this Ag in alum, although the magnitude of their responses is much reduced in comparison with those of Cr2(+/-) and C57BL/6 controls. Increasing Ag dose partially corrected this deficit. In situ study of the somatic genetics of GC B cells demonstrated that VDJ hypermutation does not require CD21/CD35, and Cr2(-/-) mice exhibited enhanced affinity maturation of serum Ab in the post-GC phase of the primary response. On the other hand, Cr2(-/-) mice displayed accelerated loss of serum Ab and long-lived Ab-forming cells. These observations suggest that B-cell activation/survival signals mediated by CD21 and/or the retention of Ag by CD21/CD35 play important roles in the generation, quality, and maintenance of serum Ab. The Journal of Immunology, 2000, 164: 4522-4532.